Document Detail


Uricosuric effect of CGS-12970, a new thromboxane synthase inhibitor.
MedLine Citation:
PMID:  8330466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
3-Methyl-2-(3-pyridyl)-1-indoleoctanoic acid (CGS-12970) is a reversible thromboxane synthase inhibitor that was noted to lower serum uric acid during preliminary trials in humans. Our clinical research unit studied 20 healthy male volunteers who received two doses of CGS-12970 12 hours apart (100, 200, 300, or 400 mg twice a day). Four subjects received placebo as a control. Serum uric acid concentrations decreased between 34% and 47%. Urinary excretion of uric acid increased between 28% and 134% within 12 hours of the first dose. Urinary excretion of uric acid returned to baseline within 24 hours after the last dose. In vitro study of bovine-creme xanthine oxidase inhibitor activity revealed minimal inhibition of xanthine oxidase by either CGS-12970 or its metabolite, CGS-12961. CGS-12970 appears to be a potent reversible uricosuric agent. We hypothesize that the uricosuric effect may be attributable to the acidic properties of CGS-12970 rather than to its inhibition of thromboxane synthase.
Authors:
S D Saris; A J Piraino; J M Morgan; W L Hirschhorn; E Meidl; A V Schaffer
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  54     ISSN:  0009-9236     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-19     Completed Date:  1993-08-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  65-9     Citation Subset:  AIM; IM    
Affiliation:
Clinical Research Unit, Medical College of Pennsylvania, Philadelphia 19129.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Animals
Cattle
Creatinine / blood,  urine
Dose-Response Relationship, Drug
Humans
Male
Middle Aged
Pyridines / pharmacology*
Reference Values
Single-Blind Method
Thromboxane-A Synthase / antagonists & inhibitors*
Uric Acid / blood*,  urine
Uricosuric Agents / pharmacology*
Xanthine Oxidase / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Pyridines; 0/Uricosuric Agents; 60-27-5/Creatinine; 69-93-2/Uric Acid; 87627-28-9/3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; EC 1.17.3.2/Xanthine Oxidase; EC 5.3.99.5/Thromboxane-A Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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